Development and validation of a random survival forest model for predicting long-term survival of early-stage young breast cancer patients based on the SEER database and an external validation cohort.

Young breast cancer (YBC) patients often face a poor prognosis, hence it's necessary to construct a model that can accurately predict their long-term survival in early stage. To realize this goal, we utilized data from the Surveillance, Epidemiology, and End Results (SEER) databases between January 2010 and December 2020, and meanwhile, enrolled an independent external cohort from Tianjin Medical University Cancer Institute and Hospital. The study aimed to develop and validate a prediction model constructed using the Random Survival Forest (RSF) machine learning algorithm. By applying the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, we pinpointed key prognostic factors for YBC patients, which were used to create a prediction model capable of forecasting the 3-year, 5-year, 7-year, and 10-year survival rates of YBC patients. The RSF model constructed in the study demonstrated exceptional performance, achieving C-index values of 0.920 in the training set, 0.789 in the internal validation set, and 0.701 in the external validation set, outperforming the Cox regression model. The model's calibration was confirmed by Brier scores at various time points, showcasing its excellent accuracy in prediction. Decision curve analysis (DCA) underscored the model's importance in clinical application, and the Shapley Additive Explanations (SHAP) plots highlighted the importance of key variables. The RSF model also proved valuable in risk stratification, which has effectively categorized patients based on their survival risks. In summary, this study has constructed a well-performed prediction model for the evaluation of prognostic factors influencing the long-term survival of early-stage YBC patients, which is significant in risk stratification when physicians handle YBC patients in clinical settings.

A multifunctional cascade enzyme system for enhanced starvation/chemodynamic combination therapy against hypoxic tumors.

Starvation therapy has shown promise as a cancer treatment, but its efficacy is often limited when used alone. In this work, a multifunctional nanoscale cascade enzyme system, named CaCO3@MnO2-NH2@GOx@PVP (CMGP), was fabricated for enhanced starvation/chemodynamic combination cancer therapy. CMGP is composed of CaCO3 nanoparticles wrapped in a MnO2 shell, with glucose oxidase (GOx) adsorbed and modified with polyvinylpyrrolidone (PVP). MnO2 decomposes H2O2 in cancer cells into O2, which enhances the efficiency of GOx-mediated starvation therapy. CaCO3 can be decomposed in the acidic cancer cell environment, causing Ca2+ overload in cancer cells and inhibiting mitochondrial metabolism. This synergizes with GOx to achieve more efficient starvation therapy. Additionally, the H2O2 and gluconic acid produced during glucose consumption by GOx are utilized by MnO2 with catalase-like activity to enhance O2 production and Mn2+ release. This process accelerates glucose consumption, reactive oxygen species (ROS) generation, and CaCO3 decomposition, promoting the Ca2+ release. CMGP can alleviate tumor hypoxia by cycling the enzymatic cascade reaction, which increases enzyme activity and combines with Ca2+ overload to achieve enhanced combined starvation/chemodynamic therapy. In vitro and in vivo studies demonstrate that CMGP has effective anticancer abilities and good biosafety. It represents a new strategy with great potential for combined cancer therapy.

Desulfurdioxidative N-N Coupling of N-Arylhydroxylamines and N-Sulfinylanilines: Reaction Development and Mechanism.

A highly efficient and chemoselective approach for the divergent assembling of unsymmetrical hydrazines through an unprecedented intermolecular desulfurdioxidative N-N coupling is developed. This metal free protocol employs readily accessible N-arylhydroxylamines and N-sulfinylanilines to provide highly valuable hydrazine products with good yields and excellent functional group tolerance under simple conditions. Computational studies suggest that the in situ generated O-sulfenylated arylhydroxylamine intermediate undergoes a retro-[2π+2σ] cycloaddition via a stepwise diradical mechanism to form the N-N bond and release SO2.

Four lathyrane diterpenoids from the seeds of Euphorbia lathyris.

Four new diterpenoids, including three secolathyrane diterpenoids (1-3) and one lathyrane diterpenoid (4), together with seven known diterpenoids, were obtained in the shelled seeds of Euphorbia lathyris. In particular, 1-3 possess a rare split ring structure, and currently only one compound with the same skeleton has been identified in E. lathyris. Compound 4 furnishes an unprecedented oxygen bridge structure. The structures were identified using various spectral techniques, including NMR, HR-ESI-MS, single-crystal X-ray diffraction and calculated electronic circular dichroism (ECD). The biosynthetic pathway of 1-4 was inferred. Furthermore, the cytotoxic activities of all compounds (1-11) were measured on three human tumor cells. New compounds 2 and 3 showed moderate cytotoxic activities against U937 cells with IC50 values of 22.18 and 25.41 µM, respectively.

ALK upregulates POSTN and WNT signaling to drive neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor of childhood. While MYCN and mutant anaplastic lymphoma kinase (ALKF1174L) cooperate in tumorigenesis, how ALK contributes to tumor formation remains unclear. Here, we used a human stem cell-based model of neuroblastoma. Mis-expression of ALKF1174L and MYCN resulted in shorter latency compared to MYCN alone. MYCN tumors resembled adrenergic, while ALK/MYCN tumors resembled mesenchymal, neuroblastoma. Transcriptomic analysis revealed enrichment in focal adhesion signaling, particularly the extracellular matrix genes POSTN and FN1 in ALK/MYCN tumors. Patients with ALK-mutant tumors similarly demonstrated elevated levels of POSTN and FN1. Knockdown of POSTN, but not FN1, delayed adhesion and suppressed proliferation of ALK/MYCN tumors. Furthermore, loss of POSTN reduced ALK-dependent activation of WNT signaling. Reciprocally, inhibition of the WNT pathway reduced expression of POSTN and growth of ALK/MYCN tumor cells. Thus, ALK drives neuroblastoma in part through a feedforward loop between POSTN and WNT signaling.

Hematoporphyrin injection mediated photodynamic therapy for secondary squamous cell carcinoma of arsenical keratosis: A case report.

Hematoporphyrin injection (HpD) mediated photodynamic therapy (PDT) has demonstrated efficacy in treating various types of Bowen's disease, including basal-cell carcinoma, squamous cell carcinoma, extramammary Paget's disease, and actinic keratosis. We present a case of a male patient who developed squamous cell carcinoma as a result of repeated instances of arsenic-induced keratosis on both his hands and feet. Due to the involvement of the joint in both hands, the patient declined the conventional surgical resection treatment since it could potentially impact normal physiological function. Instead, the patient chose to undergo hemoporphyrin photodynamic therapy. After the treatment, the rash was entirely eliminated and there were no restrictions in the movement of the joint. Nevertheless, a local recurrence was detected throughout the two-year monitoring period. Arsenical keratosis carries a substantial likelihood of recurring. However, we believe that hemoporphyrin photodynamic therapy is effective in treating this condition.

Involvement of GSTP1 in low dose radiation-induced apoptosis in GM12878 cells.

BACKGROUND: Low-dose ionizing radiation-induced protection and damage are of great significance among radiation workers. We aimed to study the role of glutathione S-transferase Pi (GSTP1) in low-dose ionizing radiation damage and clarify the impact of ionizing radiation on the biological activities of cells. RESULTS: In this study, we collected peripheral blood samples from healthy adults and workers engaged in radiation and radiotherapy and detected the expression of GSTP1 by qPCR. We utilized γ-rays emitted from uranium tailings as a radiation source, with a dose rate of 14 µGy/h. GM12878 cells subjected to this radiation for 7, 14, 21, and 28 days received total doses of 2.4, 4.7, 7.1, and 9.4 mGy, respectively. Subsequent analyses, including flow cytometry, MTS, and other assays, were performed to assess the ionizing radiation's effects on cellular biological functions. In peripheral blood samples collected from healthy adults and radiologic technologist working in a hospital, we observed a decreased expression of GSTP1 mRNA in radiation personnel compared to the healthy controls. In cultured GM12878 cells exposed to low-dose ionizing radiation from uranium tailings, we noted significant changes in cell morphology, suppression of proliferation, delay in cell cycle progression, and increased apoptosis. These effects were partially reversed by overexpression of GSTP1. Moreover, low-dose ionizing radiation increased GSTP1 gene methylation and downregulated GSTP1 expression. Furthermore, low-dose ionizing radiation affected the expression of GSTP1-related signaling molecules. CONCLUSIONS: This study shows that low-dose ionizing radiation damages GM12878 cells and affects their proliferation, cell cycle progression, and apoptosis. In addition, GSTP1 plays a modulating role under low-dose ionizing radiation damage conditions. Low-dose ionizing radiation affects the expression of Nrf2, JNK, and other signaling molecules through GSTP1.

Emerging role of RNA modification and long noncoding RNA interaction in cancer.

RNA modification, especially N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine methylation, participates in the occurrence and progression of cancer through multiple pathways. The function and expression of these epigenetic regulators have gradually become a hot topic in cancer research. Mutation and regulation of noncoding RNA, especially lncRNA, play a major role in cancer. Generally, lncRNAs exert tumor-suppressive or oncogenic functions and its dysregulation can promote tumor occurrence and metastasis. In this review, we summarize N6-methyladenosine, 5-methylcytosine, and N7-methylguanosine modifications in lncRNAs. Furthermore, we discuss the relationship between epigenetic RNA modification and lncRNA interaction and cancer progression in various cancers. Therefore, this review gives a comprehensive understanding of the mechanisms by which RNA modification affects the progression of various cancers by regulating lncRNAs, which may shed new light on cancer research and provide new insights into cancer therapy.

Structural insight into subunit F of respiratory chain complex I from Xanthomonas oryzae pv. oryzae inhibition by parthenolide.

BACKGROUND: Bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most serious diseases of rice, and there is a lack of bactericides for controlling this disease. We previously found parthenolide (PTL) is a potential lead for developing bactericides against Xoo, and subunit F of respiratory chain complex I (NuoF) is an important target protein of PTL. However, the binding modes of PTL with NuoF need further elucidation. RESULTS: In this study, we obtained the crystal structure of Xoo NuoEF (complex of subunit E and F of respiratory chain complex I) with a resolution of 2.36 Å, which is the first report on the protein structure of NuoEF in plant-pathogenic bacteria. The possible binding sites of PTL with NuoF (Cys105 and Cys187) were predicted with molecular docking and mutated into alanine using a base mismatch method. The mutated proteins were expressed in Escherichia coli and purified with affinity chromatography. The binding abilities of PTL with mutated proteins were investigated via pull-down assay and BIAcore analysis, which revealed that double mutation of Cys105 and Cys187 in NuoF severely affected the binding ability of PTL with NuoF. In addition, the binding modes were further simulated with combined quantum mechanical/molecular mechanical calculations, and the results indicated that PTL may have a stronger binding with Cys105 than Cys187. CONCLUSION: NuoEF protein structure of Xoo was resolved, and Cys105 and Cys187 in NuoF are important binding sites of PTL. This study further clarified the action mechanism of PTL against Xoo, and will promote the innovation of bactericides targeting Xoo complex I. © 2024 Society of Chemical Industry.

Identification of One O-Methyltransferase Gene Involved in Methylated Flavonoid Biosynthesis Related to the UV-B Irradiation Response in Euphorbia lathyris.

Flavonoids are ubiquitous polyphenolic compounds that play a vital role in plants' defense response and medicinal efficacy. UV-B radiation is a vital environmental regulator governing flavonoid biosynthesis in plants. Many plants rapidly biosynthesize flavonoids as a response to UV-B stress conditions. Here, we investigated the effects of flavonoid biosynthesis via UV-B irradiation in Euphorbia lathyris. We found that exposure of the E. lathyris callus to UV-B radiation sharply increased the level of one O-methyltransferase (ElOMT1) transcript and led to the biosynthesis of several methylated flavonoids. The methyltransferase ElOMT1 was expressed heterologously in E. coli, and we tested the catalytic activity of recombinant ElOMT1 with possible substrates, including caffeic acid, baicalin, and luteolin, in vitro. ElOMT1 could efficiently methylate when the hydroxyl groups were contained in the core nucleus of the flavonoid. This molecular characterization identifies a methyltransferase responsible for the chemical modification of the core flavonoid structure through methylation and helps reveal the mechanism of methylated flavonoid biosynthesis in Euphorbiaceae. This study identifies the O-methyltransferase that responds to UV-B irradiation and helps shed light on the mechanism of flavonoid biosynthesis in Euphorbia lathyris.

Achieving High Initial Coulombic Efficiency and Capacity in a Surface Chemical Grafting Layer of Plateau-type Sodium Titanate.

The plateau-type sodium titanate with suitable sodiation potential is a promising anode candidate for high safe and high energy density of sodium-ion batteries (SIBs). However, the poor initial Coulombic efficiency (ICE) and cyclic instability of sodium titanate are attributed to the unstable interfacial structure along with the decomposition of electrolytes, resulting in the continuous formation of solid electrolyte interface (SEI) film. To address this issue, a chemical grafting method is developed to fabricate a highly stable interface layer of inert Al2 O3 on the sodium titanate anode, rendering the high ICE and excellent cycling stability. Based on theoretical calculations, NaPF6 are more likely adsorption on the Al2 O3 surface and produce sodium fluoride. The formation of a thin and dense SEI film with rich sodium fluoride achieves the low interfacial resistances and charge-transfer resistances. Benefitting from our design, the obtained sodium titanate exhibits a high ICE from 67.7 % to 79.4 % and an enhanced reversible capacity from 151 mAh g-1 to 181 mAh g-1 at 20 mA g-1 , along with an increase in capacity retention from 56.5 % to 80.6 % after 500 cycles. This work heralds a promising paradigm for rational regulation of interfacial stability to achieve high-performance anodes for SIBs.

Antifungal activity of the botanical compound rhein against Phytophthora capsici and the underlying mechanisms.

BACKGROUND: Phytophthora capsici is an extremely destructive phytopathogenic oomycete that causes huge economic losses. However, due to the drug resistance risk and environmental threat of chemical fungicides, it is necessary to develop environmentally friendly biocontrol alternatives. Rhein is a major medicinal ingredient of traditional Chinese herbs, and it is widely used in the medical field. However, its inhibitory effect against phytopathogens is unknown. Herein, the antifungal spectrum of rhein and its possible action mechanism against P. capsici were investigated. RESULTS: Rhein possessed broad-spectrum antifungal activity against phytopathogens, particularly P. capsici, Phytophthora infestans, Helminthosporium maydis, and Rhizoctonia solani. Rhein inhibited the mycelial growth as well as the spore germination of P. capsici with mean 50% effective concentration (EC50 ) values of 4.68 µg mL-1 and 6.57 µg mL-1 against 117 P. capsici isolates, respectively. Rhein effectively suppressed the occurrence and spread of Phytophthora blight and significantly destroyed the cell membrane permeability and integrity of P. capsici, corroded its cell wall integrity, and damaged its morphology and ultrastructure. Moreover, rhein caused a considerable reduction in the phospholipid and cellulose contents. Genome-wide transcriptional profiling of P. capsici in response to rhein indicated significant reduction in the expression levels of genes participating in glycerolipid metabolism and starch and sucrose metabolism. Additionally, rhein strengthened the disease defense system of pepper by enhancing related enzyme activities. CONCLUSION: This study demonstrated that rhein could effectively inhibit P. capsici using multiple mechanisms of action. Rhein has the potential to be an efficient alternative to control diseases caused by P. capsici. © 2023 Society of Chemical Industry.

Alveolar bone remodelling and stability of mandibular incisors in adult patients after orthodontic treatment with premolar extractions: A prospective follow-up study.

OBJECTIVE: To evaluate alveolar bone remodelling and stability of mandibular incisors in adult orthodontic extraction patients. MATERIALS AND METHODS: Cone-beam computed tomography images of 25 adult patients undergoing extraction were collected before orthodontic treatment (T1), after orthodontic treatment (T2), and after at least 1 year of retention (T3). The labial and lingual alveolar bone heights (ABH), thickness (ABT), and tooth movement of the mandibular incisors were measured during the retraction (T2-T1) and retention (T3-T2) periods. According to the tooth movement during the retention period, the mandibular incisors were further divided into stable and unstable groups, and the correlation between L1-BMe and stability was evaluated. RESULTS: The labial and lingual ABHs significantly increased after orthodontic treatment and decreased during the retention period. The lingual ABH was 7.36 ± 2.27 mm at T2 and 5.37 ± 1.98 mm at T3, indicating a great bone remodelling capacity. The labial ABT exhibited a significant increase during orthodontic treatment and a slight decrease during the retention period, while the lingual ABT showed an opposite trend. During the retention period, the root apex moved labially into the alveolar bone housing. L1-BMe significantly increased during orthodontic treatment and decreased during the retention period. Compared to the stable group, lingual ABH and L1-BMe at T2 was significantly higher, and lingual ABT was smaller in the unstable group. CONCLUSION: Post-treatment lingual alveolar bone defects of the mandibular incisors could recover to some extent during the retention period. There was a negative correlation between post-treatment L1-BMe and mandibular incisor stability.

Association between imaging parameter changes and triangular fibrocartilage complex injury after distal radius fractures.

BACKGROUND: Triangular fibrocartilage complex (TFCC) injury is a frequent soft tissue injury that has been observed to accompany distal radius fractures (DRFs) with concomitant changes in radiologic parameters. The aim of this study was to investigate the relevance of distal radial radiologic parameters associated with DRF and traumatic TFCC injury. METHODS: A total of 172 patients with distal radius fractures who underwent X-ray, CT, and MRI before undergoing volar locking plate or external splint fixation between October 2021 and December 2022 were included in this study. An analysis of various radiologic parameters and the classification of fracture type and TFCC injuries by CT and MRI was performed. All patients were divided into the TFCC uninjured group and the injured group. The incidence and relevant radiologic parameters were compared. RESULTS: This study included 76 males and 96 females with a mean age of 56.1 years. Among all patients, 33 (19.2%), 40 (23.2%), and 99 (57.6%) had DRF with A, B, and C fractures, respectively, according to the AO/OTA classification. In patients with fractures, the TFCC was found to be injured in 54.1% (93/172) of patients (type 1A in 21, 1B in 46, 1C in 39, and 1D in 35) but uninjured in 45.9% (79/172). There were significant differences between the TFCC injured and uninjured groups regarding the radius length (p = 0.044) and DRUJ distance (p = 0.040) of radiologic parameters that changed with DRF, although there were no differences between the two groups regarding gender, age, injured side, intra- and extra-articular, radius inclination and palmer tilt angle, or sagittal translation. Within the TFCC injured group, the radius length and DRUJ distance were 4.83 mm and 2.95 mm less or wider than 7.19 mm and 1.83 mm of the uninjured group. Moreover, shorter radius length was related to type lB TFCC injury (p = 0.041). Both radius length (AUC = 0.658) and DRUJ distance (AUC = 0.582) had no convincing predictive value for TFCC injury in DRF. CONCLUSION: 1B TFCC injury is most common in patients with DRF and concomitant TFCC injury. Both radius length and DRUJ distance have a significant statistical correlation with TFCC injury, and patients with TFCC injury tend to have a shortened radius and wider DRUJ distance, although they have no predictive value for TFCC injury in DRF. In addition, a shorter radius length was related to type lB TFCC injury.

Identification and Functional Characterization of a Novel Sinapyl Alcohol Acyltransferase from Euphorbia lathyris L.

Methoxyeugenol is a phenylpropene compound derived from plants and has various bioactivities. The chemical synthesis of methoxyeugenol is accompanied by pollution issues, whereas extraction from plants is associated with problems such as low yield and high cost. The production of methoxyeugenol can be effectively addressed through an enzymatic approach. In this study, the acyltransferase genes of Euphorbia lathyris L. were screened by homologous alignment of the transcriptome data of E. lathyris in the late growth stage and the acyltransferase genes of the closely related plant species. The results showed that ElBAHD10 had the closest relationship with earlier reported ScCFAT and PhCFAT, which were found to catalyze the reaction of coniferyl alcohol to generate coniferyl acetate. The ElBAHD10 gene was successfully cloned from E. lathyris and subsequently expressed in Escherichia coli. The purified protein ElBAHD10 catalyzed the reaction of sinapyl alcohol with acetyl CoA and cinnamoyl CoA to form sinapyl acetate and sinapyl cinnamate, respectively. In contrast, the crude ElBAHD10 protein could catalyze sinapyl alcohol to directly generate methoxyeugenol. The recombinant E. coli strain expressing ElBAHD10 produced methoxyeugenol through whole-cell transformation. This study provides insights and lays the foundation for methoxyeugenol production through biosynthetic approaches.

GSDMD inhibitor protects chondrocyte from mechanical injury in human articular cartilage.

Traumatic arthritis is caused by mechanical injury and results in the degeneration of articular cartilage, but it is unclear whether it is related to the pyroptosis of chondrocyte (CHs). Thus, this study was designed to investigate the role of GSDMD, the executor of pyroptosis, in the human cartilage during mechanical injury. We collected the human hip joint and used a loading apparatus to produce compression on the cartilage disc. After one hour of 15 MPa or 25 MPa injury, the acute and chronic effects of the mechanical injury on the cartilage were tested. We stained the CHs in the cartilage with calcein and DAPI to calculate the live-cell rate. The chondrogenic phenotype was determined by analyzing the mRNA levels of type II collagen alpha 1 (Col2A1), type I collagen alpha 2 (Col2A1), and SOX9. Besides, the pyroptosis process was determined by the mRNA levels of caspase-1/5, GSDMD, IL-1ß, and IL-18. We also explored the preventive role and therapeutic role of GSDMD inhibitors in mechanical injury via culturing the cartilage before and after the compression, respectively. Mechanical compression injured the viability and function of CHs in cartilage partly based on the pyroptosis. The pretreatment of GSDMD inhibitor in cartilage before injury could maintain the live cells and Col2A1 expression and prevent pyroptosis after injury. Besides, supplying the cartilage with GSDMD inhibitor after injury also alleviated the cell death and dysfunction of CHs, and suppressed the pyroptosis. Using an inhibitor of GSDMD can play a preventive role and play a therapeutic role in the mechanical injury of cartilage.

Long-term bone remodeling of maxillary anterior teeth with post-treatment alveolar bone defect in adult patients with maxillary protrusion: a prospective follow-up study.

BACKGROUND: Alveolar bone defects, particularly palatal bone dehiscence (PBD) and labial bone fenestration (LBF), occur frequently as a result of retraction of the maxillary anterior teeth. The study aims to explore the long-term bone remodeling of maxillary anterior teeth in adult patients with post-orthodontic treatment PBD and LBF. MATERIALS AND METHODS: The study includes 24 adult patients with maxillary protrusion (8 males, 16 females) who were treated with extraction of four first premolars and had alveolar bone defects (PBD or LBF) in maxillary anterior teeth following orthodontic treatment. Cone-beam computed tomography imaging measurements were obtained before (T1), after (T2) orthodontic treatment, and after at least 1-year removable thermoplastic retainer retention (T3). The maxillary anterior teeth with PBD or LBF at T2 were divided into the PBD or LBF groups, respectively. The labial and palatal alveolar bone height (ABH), alveolar bone thickness (ABT), and movement of maxillary anterior teeth were measured during retraction (T2-T1) and retention (T3-T2) periods. RESULTS: The incidence of PBD and LBF in maxillary anterior teeth significantly increased after orthodontic treatment and decreased during the retention period. In the PBD group, the palatal ABH of all maxillary anterior teeth significantly increased from T1 to T2 but decreased from T2 to T3. The ABT of the maxillary central incisor and canine significantly increased on the palatal side and decreased on the labial side during the retention period. In the LBF group, the labial ABT of the maxillary central incisor at the apical level showed a significant decrease from T1 to T2, followed by an increase from T2 to T3. In both groups, the maxillary central incisor showed significant labial movement, with a relative intrusion during the retention period. CONCLUSION: For adult patients with maxillary protrusion, the alveolar bone defect of maxillary anterior teeth caused by orthodontic retraction significantly improved during the retention period, indicating good long-term bone remodeling. Our findings suggest that a combination of spontaneous reorientation of maxillary anterior teeth and bone remodeling contributed to alveolar bone covering in these patients.

Assessing the Relationship between Prosocial Behavior and Well-Being: Basic Psychological Need as the Mediator.

Previous research has established a positive link between prosocial behavior (PB) and psychological well-being. However, limited studies have explored the relationship between PB and well-being (WB), particularly among vocational students. Furthermore, the underlying mechanisms, including mediating factors, remain understudied in this context. This study aimed to investigate the association between PB and WB among vocational students while examining the mediating role of basic psychological needs. A sample of 221 vocational students (mean age = 19.68 years, SD = 1.57) completed anonymous questionnaires assessing PB, basic psychological needs, and WB. The results revealed a positive correlation between PB and WB in vocational students (r = 0.22, p < 0.01), with basic psychological needs partially mediating this relationship (ß = 0.14, t = 10.85, p < 0.001, 95% CI = (0.18, 0.23)). These findings enhance our understanding of the association between PB and vocational students' WB, shed light on the mechanisms involved, and offer insights into promoting the well-being of vocational students.

An Updated Review on Developing Small Molecule Kinase Inhibitors Using Computer-Aided Drug Design Approaches.

Small molecule kinase inhibitors (SMKIs) are of heightened interest in the field of drug research and development. There are 79 (as of July 2023) small molecule kinase inhibitors that have been approved by the FDA and hundreds of kinase inhibitor candidates in clinical trials that have shed light on the treatment of some major diseases. As an important strategy in drug design, computer-aided drug design (CADD) plays an indispensable role in the discovery of SMKIs. CADD methods such as docking, molecular dynamic, quantum mechanics/molecular mechanics, pharmacophore, virtual screening, and quantitative structure-activity relationship have been applied to the design and optimization of small molecule kinase inhibitors. In this review, we provide an overview of recent advances in CADD and SMKIs and the application of CADD in the discovery of SMKIs.

177 Lu-FAP-2286 Therapy in a Case of Recurrent Bladder Cancer With Multiple Metastatic Lesions.

ABSTRACT: We reported a 73-year-old man who was diagnosed with the recurrence of bladder tumor received 177 Lu-FAP-2286 treatment. Encouragingly, radiological remission and alleviation of his symptom were noted. In addition, the patient did not have any adverse effects.